NM_000124.4(ERCC6):c.2989A>G (p.Lys997Glu) AND Cockayne syndrome type 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 8, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000338857.6

Allele description [Variation Report for NM_000124.4(ERCC6):c.2989A>G (p.Lys997Glu)]

NM_000124.4(ERCC6):c.2989A>G (p.Lys997Glu)

Gene:

ERCC6:ERCC excision repair 6, chromatin remodeling factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q11.23

Genomic location:

Preferred name:

NM_000124.4(ERCC6):c.2989A>G (p.Lys997Glu)

HGVS:

NC_000010.11:g.49471056T>C
NG_009442.1:g.73046A>G
NM_000124.4:c.2989A>GMANE SELECT
NM_001346440.2:c.2989A>G
NP_000115.1:p.Lys997Glu
NP_001333369.1:p.Lys997Glu
LRG_465:g.73046A>G
NC_000010.10:g.50679102T>C
NM_000124.3:c.2989A>G

Protein change:

K997E

Links:

dbSNP: rs375181157

NCBI 1000 Genomes Browser:

rs375181157

Molecular consequence:

NM_000124.4:c.2989A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001346440.2:c.2989A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cockayne syndrome type 2 (CSB)
Synonyms:: Cockayne syndrome B; Cockayne syndrome type 2; Cockayne Syndrome, Type II
Identifiers:: MONDO: MONDO:0019570; MedGen: C0751038; Orphanet: 191; OMIM: 133540

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000362826	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV001573385	Ocular Genomics Institute, Massachusetts Eye and Ear	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 8, 2021)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000362826

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV001573385

Ocular Genomics Institute, Massachusetts Eye and Ear

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 8, 2021)

germline

research

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000362826.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ocular Genomics Institute, Massachusetts Eye and Ear, SCV001573385.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

Description

The ERCC6 c.2989A>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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